In order to prevent central nervous system injury in the newborn resulting from unconjugated hyperbilirubinemia (kernicterus), the mechanisms responsible for physiologic jaundice in the neonate and for transfer of bilirubin from plasma into the brain must be more fully understood. Extensive work from this laboratory and others has shown that physologic jaundice results from a complex interaction between increased bilirubin load and decreased hepatic conjugation and uptake of bilirubin. The present studies concentrate on examining the contribution of enteric bilirubin absorbtion in the new born as a source for the increased bilirubin load. Data from newborn rhesus monkeys has shown that the enteric source is the major one after the first week of life and up to the sixth week, after which there is no increased load. Certain free fatty acids have been shown in adult rats to either enhance or diminish enteric bilirubin absorbtion. Studies of the role of fatty acids and bile salts are now being undertaken to determine the contribution of these factors to enteric bilirubin absorbtion in the newborn. Certain free ftty acids have been shown by several independent methods to form complexes with unconjugated bilirubin, altering measurement of bilirubin binding to albumin and providing a non-albumin transfer of bilirubin. The contributin of this role of free fatty acids to the risk of kernicterus is being examined both in vitro and in vivo. Late pregnant and early neonatal hepatic conjugating mechanisms have been shown to be relatively resistant to induction by phenobarbital. The mechanism of this resistance to induction is being investigated using metal ions and hepatic cell fractionation. The ultimate aim of this proposal is the development of sufficient understanding of developmental deficiencies in bilirubin metabolism and transport in the newborn to permit pharmacologic and dietary manipulations which will mitigate against bilirubin accumulation and kernicterus.